BIOLOGY OF OVARIAN CANCER PROGRAM PROJECT

卵巢癌生物学计划项目

• 批准号: 2330896
• 负责人: ROBERT B JAFFE
• 金额: $ 140.42万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-04-15 至 2000-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2330896
• 关键词: female; neoplastic process; ovary neoplasms; vascular endothelial growth factors

The overall goal of the proposed project grant (PPG) is to assemble an interdisciplinary group of talented investigators from different fields to study the biology of ovarian cancer. The general theme of the PPG deals with the growth aspects of ovarian tumor progression. The hypothesis to be addressed is that the onset and progression of ovarian tumors is dependent on aspects of growth regulation (i.e., genetic aberrations, stromal environment, angiogenesis, and local growth facto production) that directly influence tumor categorization, grade and stage. The present application consists of 4 interdisciplinary individual research projects and three core facilities. Project 1. (Michael Skinner) investigates cell-cell interactions and ovarian cancer. The hypothesis tested is that ovarian surface epithelial cells. (OSE) are regulated by mesenchymal (stromal)-epithelial cell interactions mediated by the local production and action of growth stimulators and growth inhibitors. Observations indicate that ovarian tumor growth is dramatically influenced by the stromal environment. The biology of normal and tumorigenic OSE will be examined. Project 2 (Robert Jaffe) investigates angiogenesis in ovarian epithelial carcinoma. The hypothesis tested is that the action of vascular endothelial growth factor (VEGF) is necessary to promote the neovascularization and tumor growth of human ovarian epithelial carcinoma. The extent of angiogenesis and expression of VEGF will also be correlated with tumor progression (i.e., tumor stage and grade). Project 3 (Joe Gray) investigates the role of allelic imbalance in ovarian cancer progression. Using analysis of loss of heterozygosity (LOH), comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH), the chromosomal mapping of common allelic imbalance will be correlated with tumor progression (i.e., tumor stage and grade). Genes will be positionally cloned in regions of common imbalance and, in collaboration with the other projects, genes of interest (e.g., growth factors and receptors) will be mapped and correlated to chromosomal maps. Project 4 (Gordon Mills) investigates a recently purified ovarian cancer ascites factor (OCAF) from ascites fluid of ovarian cancer patients and its role in tumor growth and progression. The hypothesis tested is that OCAF produced by ovarian cancer cells plays a role in tumorigenesis by increasing proliferation of ovarian cancer cells, decreasing sensitivity to chemotherapy, and altering immune responsiveness. These research activities will be supported by the Administrative Core for the coordination and management of the PPG. Thr Molecular Cytometry Core will provide chromosomal mapping (i.e., LOH, CGH and FISH) and technical assistance with FISH of tissue sections. The Tissue/Pathology Core, directed by Bethan Powell, will collect, catalog, and prepare human ovarian cancer surgical specimens and cell-lines for the proposed research. The integrated activities of the four projects and investigators provides a comprehensive examination of the biology of ovarian cancer with emphasis on the growth aspects of tumor progression. Observations are anticipated to provide insight into the future design of more effective therapeutic agents for the prevention, early diagnosis and treatment of ovarian cancer.

拟议项目拨款 (PPG) 的总体目标是组建一个 由来自不同领域的才华横溢的研究人员组成的跨学科团队 研究卵巢癌的生物学。 PPG 交易的总体主题 与卵巢肿瘤进展的生长方面有关。 假设为 所要解决的问题是，卵巢肿瘤的发生和进展取决于 生长调节方面（即遗传畸变、基质 环境、血管生成和局部生长因子的产生） 直接影响肿瘤的分类、分级和分期。 现在的 申请由4个跨学科个人研究项目组成 以及三大核心设施。 项目 1.（Michael Skinner）调查 细胞间相互作用和卵巢癌。 检验的假设是 卵巢表面上皮细胞。 (OSE) 受间充质调节 由局部产生和介导的（基质）-上皮细胞相互作用 生长刺激剂和生长抑制剂的作用。 观察表明 卵巢肿瘤的生长受到间质的显着影响 环境。 将检查正常和致瘤性 OSE 的生物学特性。 项目 2（Robert Jaffe）研究卵巢上皮的血管生成 癌。 所检验的假设是血管的作用 内皮生长因子（VEGF）对于促进 人卵巢上皮癌的新血管形成和肿瘤生长。 血管生成的程度和VEGF的表达也会相关 与肿瘤进展（即肿瘤分期和级别）有关。 项目 3（乔·格雷） 研究等位基因失衡在卵巢癌进展中的作用。 使用杂合性丢失（LOH）分析、比较基因组 杂交（CGH）和荧光原位杂交（FISH） 常见等位基因不平衡的染色体作图将与 肿瘤进展（即肿瘤分期和级别）。 基因将是 在共同不平衡的区域进行位置克隆，并进行协作 与其他项目一起，感兴趣的基因（例如，生长因子和 受体）将被绘制并与染色体图谱相关。 项目4 （戈登·米尔斯）研究了最近纯化的卵巢癌腹水 卵巢癌患者腹水因子（OCAF）及其在卵巢癌患者腹水中的作用 肿瘤的生长和进展。 测试的假设是 OCAF 产生 卵巢癌细胞通过增加 卵巢癌细胞增殖，降低对卵巢癌细胞的敏感性 化疗和改变免疫反应。 这些研究 活动将得到行政核心的支持 PPG 的协调和管理。 Thr 分子细胞计数核心将 提供染色体作图（即 LOH、CGH 和 FISH）和技术 协助组织切片的 FISH。 组织/病理学核心， 由 Bethan Powell 指导，将收集、编目和准备人类卵巢 用于拟议研究的癌症手术标本和细胞系。 这 四个项目和研究人员的综合活动提供了 卵巢癌生物学的全面检查，重点是 肿瘤进展的生长方面。 预计观察结果 为更有效的治疗药物的未来设计提供见解 用于卵巢癌的预防、早期诊断和治疗。